Klimov D K, Betancourt M R, Thirumalai D
Institute for Physical Science and Technology and Department of Chemistry and Biochemistry, University of Maryland, College Park 20742, USA.
Fold Des. 1998;3(6):481-96. doi: 10.1016/s1359-0278(98)00065-0.
The most conspicuous feature of a right-handed alpha helix is the presence of hydrogen bonds between the backbone carbonyl oxygen and NH groups along the chain. A simple off-lattice model that includes hydrogen bond interactions using virtual atoms is used to examine the stability, cooperativity and kinetics of the helix-coil transition.
We have studied the thermodynamics (using multiple histogram method) and kinetics (by Brownian dynamics simulations) of 16-mer minimal off-lattice models of four-turn alpha-helix sequences. The carbonyl and NH groups are represented as virtual moieties located between two alpha-carbon atoms along the polypeptide chain. The characteristics of the native conformations of the model helices, such as the helical pitch and angular correlations, coincide with those found in real proteins. The transition from coil to helix is quite broad, which is typical of these finite-sized systems. The cooperativity, as measured by a dimensionless parameter, omegac, that takes into account the width and the slope of the transition curves, is enhanced when hydrogen bonds are taken into account. The value of omegac for our model is consistent with that inferred from experiment for an alanine-based helix-forming peptide. The folding time tauF ranges from 6 to 1000 ns in the temperature range 0.7-1.9 T(F), where T(F) is the helix-coil transition temperature. These values are in excellent agreement with the results from recent fast folding experiments. The temperature dependence of tauF exhibits a nearly Arrhenius behavior. Thermally induced unfolding occurs on a time scale that is less than 40-170 ps depending on the final temperature. Our calculations also predict that, although tauF can be altered by changes in the sequence, the dynamic range over which such changes take place is not as large as that predicted for beta-turn formation.
Hydrogen bonds not only affect the stability of alpha-helix formation but also have profound influence on the kinetics. The excellent agreement between our calculations and experiments suggests that these models can be used to investigate the effects of sequence, temperature and viscosity on the helix-coil transition.
右手α螺旋最显著的特征是沿着链的主链羰基氧和NH基团之间存在氢键。使用一个简单的非晶格模型，该模型通过虚拟原子包含氢键相互作用，来研究螺旋-线团转变的稳定性、协同性和动力学。
我们研究了四圈α螺旋序列的16聚体最小非晶格模型的热力学（使用多重直方图方法）和动力学（通过布朗动力学模拟）。羰基和NH基团由沿着多肽链位于两个α碳原子之间的虚拟部分表示。模型螺旋天然构象的特征，如螺旋螺距和角度相关性，与真实蛋白质中的特征一致。从线团到螺旋的转变相当宽泛，这是这些有限尺寸系统的典型特征。当考虑氢键时，通过一个无量纲参数omegac衡量的协同性增强，omegac考虑了转变曲线的宽度和斜率。我们模型的omegac值与基于丙氨酸的螺旋形成肽的实验推断值一致。在0.7 - 1.9 T(F)的温度范围内，折叠时间tauF在6到1000纳秒之间，其中T(F)是螺旋-线团转变温度。这些值与最近快速折叠实验的结果非常吻合。tauF的温度依赖性表现出近乎阿仑尼乌斯行为。热诱导解折叠发生的时间尺度小于40 - 170皮秒，这取决于最终温度。我们的计算还预测，尽管tauF可以通过序列变化而改变，但这种变化发生的动态范围不像β转角形成所预测的那么大。
氢键不仅影响α螺旋形成的稳定性，而且对动力学有深远影响。我们的计算与实验之间的良好吻合表明，这些模型可用于研究序列、温度和粘度对螺旋-线团转变的影响。
